Article
Immunology
Ashti M. Shah, Ruben Zamora, Sebastian Korff, Derek Barclay, Jinling Yin, Fayten El-Dehaibi, Timothy R. Billiar, Yoram Vodovotz
Summary: Trauma/hemorrhagic shock followed by resuscitation leads to inflammation and organ dysfunction, with TLR4 playing a role in binding damage-associated molecular pattern molecules. TLR4-null mice showed more localized expression of inflammatory mediators compared to wild type mice. IL-17A showed positive correlations with GM-CSF, IL-10, and TNF in the kidney and gut.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Food Science & Technology
Xiaoying Tian, Xi Liang, Hong He, Qingyu Cui, Qiqi Liu, Rongbo Fan, Tongjie Liu, Huaxi Yi, Pimin Gong, Qingzhu Wang, Lanwei Zhang
Summary: Food allergy has become a global public health problem, and probiotic supplementation shows potential in preventing it. This study identified strains with good abilities in alleviating food allergy and demonstrated that oral administration of Bifidobacterium animalis KV9 (KV9) and Lactobacillus vaginalis FN3 (FN3) can attenuate allergic responses in mice. The anti-allergic activities of KV9 and FN3 are mediated through the activation of the TLR4 pathway and modulation of the expression of IRF-1 and IRF-4, resulting in a balance of Th1/Th2 cell immunology.
MOLECULAR NUTRITION & FOOD RESEARCH
(2023)
Review
Rheumatology
Yvonne L. Bartels, Peter L. E. M. van Lent, Peter M. van der Kraan, Arjen B. Blom, Kimberly M. Bonger, Martijn H. J. van den Bosch
Summary: Local and systemic low-grade inflammation, particularly involving the innate immune system, plays a significant role in the development of osteoarthritis (OA). Toll-like receptor 4 (TLR4) is a crucial receptor responsible for initiating this inflammatory response. Various ligands for TLR4, including damage-associated molecular patterns (DAMPs), can activate TLR4 signaling in the joint, resulting in the production of pro-inflammatory and catabolic mediators that contribute to joint damage. This review discusses the role of TLR4 ligands and signaling in OA, as well as different methods to inhibit TLR4 signaling and their potential applications and challenges in dampening inflammation in OA.
Review
Oncology
Mai Mahmoud Gabr, Iqira Saeed, Jared A. Miles, Benjamin P. Ross, Paul Nicholas Shaw, Markus W. Hollmann, Marie-Odile Parat
Summary: Recent evidence suggests that opioids can interact with the Toll-like receptor 4 (TLR4) on innate immune and cancer cells, potentially influencing tumor growth and metastasis. Opioids have been shown to weakly activate TLR4 and can inhibit its activation by lipopolysaccharide (LPS). The interaction of opioids with TLR4 is complex, involving non-competitive mechanisms and downstream effects on NF-kappa B activation.
Article
Biochemistry & Molecular Biology
Haein Lee, Eunha Kim, Seyun Kim
Summary: In response to LPS stimulation, the levels of IPMK in macrophages decrease due to the binding of miR-181c to the 3'UTR of IPMK mRNA, which leads to the suppression of TLR4 signaling and inflammation. Deletion of the miR-181c-binding site prevents the downregulation of IPMK levels and reduces the activation of TRAF6 and the expression of proinflammatory cytokines.
Article
Pharmacology & Pharmacy
Hong Liang, William R. Lykins, Emilie Seydoux, Jeffrey A. Guderian, Tony Phan, Christopher B. Fox, Mark T. Orr
Summary: Adjuvants are important in vaccine formulations and can activate TLR4, including phospholipid DMPC. These findings may have implications for off-target immune responses in pharmaceutical development.
Review
Pharmacology & Pharmacy
Cong Lin, Hongshuang Wang, Miyuan Zhang, Sanam Mustafa, Yibo Wang, Hongyuan Li, Hang Yin, Mark R. Hutchinson, Xiaohui Wang
Summary: Biased pharmacological modulators offer potential therapeutic benefits by targeting specific receptors with increased efficiency and reduced adverse effects. While biased signaling modulators targeting GPCRs have received attention, the modulation of non-GPCR receptors remains to be explored, including Toll-like receptor 4 (TLR4). Discovery of biased modulators of TLR4 not only provides insights for future development but also potential drug candidates for other non-GPCR receptors.
PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Biochemistry & Molecular Biology
Li Liu, Youde Jiang, Jena Steinle
Summary: The study demonstrates that Epac1 can reduce TLR4 signaling in the retina and in retinal endothelial cells, while direct inhibition of TLR4 can protect the retina against diabetes-induced changes in permeability and cell numbers.
Article
Biochemistry & Molecular Biology
Bilal Ahmad, Maria Batool, Moon-Suk Kim, Sangdun Choi
Summary: The study investigated the TLR4 antibody-binding epitopes using a computational-driven approach, identifying key residues impacting antibody affinity and TLR4 structural integrity, as well as predicting a novel epitope. This technique enhances understanding of antibody-antigen interactions and facilitates the development of new monoclonal antibodies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Zhi-Dong Zhang, Hong-Xu Li, Hu Gan, Zhen Tang, Yu-Yao Guo, Shu-Qi Yao, Tianzi Liuyu, Bo Zhong, Dandan Lin
Summary: This study demonstrates that the E3 ubiquitin ligase RNF115 inhibits the post-ER trafficking of Toll-like receptors (TLRs) by catalyzing the ubiquitination of RAB1A and RAB13. The chaperones 14-3-3 bind to phosphorylated RNF115 and facilitate its localization on the ER and Golgi apparatus. This finding provides insights into the regulatory mechanism of TLRs' post-ER trafficking.
Article
Multidisciplinary Sciences
Lijing Su, Muhammad Athamna, Ying Wang, Junmei Wang, Marina Freudenberg, Tao Yue, Jianhui Wang, Eva Marie Y. Moresco, Haoming He, Tsaffrir Zor, Bruce Beutler
Summary: Sulfatides can activate mouse immune responses via the TLR4-MD-2 complex, but exhibit antagonistic effects in human cells. Their activity is related to the presence of the sulfate group and the length of the fatty acid chain, and their structure mimics the activation mechanism of molecules like LPS in receptors.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Chemistry, Medicinal
Yongsheng Zhang, Xinjie Liang, Xuefei Bao, Wei Xiao, Guoliang Chen
Summary: This review discusses TLR4 inhibitors that can bind directly to TLR4 or the TLR4/MD2 complex, as well as compounds that can downregulate the expression of TLR4. The involvement of specific residues in the binding of antagonistic ligands to the TLR4/MD2 complex provides useful information for structure-based TLR4 inhibitor design.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Feng-Ming Yang, Hui-Ming Chang, Edward T. H. Yeh
Summary: The study reveals that protein phosphatase 4 (PP4) acts as a specific phosphatase for sNASP, negatively regulating TLR4-induced TRAF6 activation. PP4 is recruited by phosphorylated sNASP to dephosphorylate it and terminate TRAF6 activation. This mechanism functions as a negative regulator of innate immunity by controlling the binding of sNASP to TRAF6.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Pathology
Tan Li, Jingjing Jing, Nannan Dong, Xiaozheng Liu, Chunyan Ma, Jun Yang
Summary: This study found a correlation between TLR4 gene polymorphisms and AA disease, with the rs1927914 polymorphism showing a significant association with TLR4 expression levels, possibly through influencing the promoter activity of TLR4.
EXPERIMENTAL AND MOLECULAR PATHOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Justin Thomas, Molly A. Torok, Kriti Agrawal, Timothy Pfau, Trang T. Vu, Justin Lyberger, Hsiaochi Chang, Alyssa Marie M. Castillo, Min Chen, Bryan Remaily, Kyeongmin Kim, Zhiliang Xie, Mary E. Dillhoff, Samuel K. Kulp, Gregory K. Behbehani, Zobeida Cruz-Monserrate, Latha P. Ganesan, Dwight H. Owen, Mitch A. Phelps, Christopher C. Coss, Thomas A. Mace
Summary: The neonatal Fc receptor (FcRn) is responsible for recycling antibodies and albumin in the body. However, little is known about its expression in circulating immune cells. In this study, FcRn expression was found to be elevated in immune cells of pancreatic ductal adenocarcinoma (PDAC) patients and mice with PDAC. These findings may contribute to understanding the mechanisms behind poor efficacy of antibody immunotherapies in PDAC patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)